Obesity is a huge and increasing medical problem, with inadequate therapeutic options. One approach to the treatment of obesity is long-term pharmacotherapy. One modestly effective drug, orlistat, has been marketed in the United States since 1999. More recently four other drugs have been approved by the FDA: lorcaserin and Qsymia (a combination of phentermine and topiramate) in 2012 and Contrave (a combination of buproprion and naltrexone) and liraglutide (high dose) in 2014. The limited efficacy of single agents has led to the idea that additional agents and combination therapy are required. Progress in FY2016 includes the following: In 2015 we reported the effects of CL316243, a beta3-adrenergic agonist studied under similar conditions (1). To our surprise, the interaction between environmental temperature and CL316243 treatment is different from the interaction between environmental temperature and 2,4-dinitrophenol treatment reported previously, suggesting that each drug mechanism must be examined to understand the effect of environmental temperature on drug efficacy. We also searched (unsuccessfully) using parabiotic mice for an endogenous ligand for Brs3 (2). Identification of such a ligand would significantly increase our knowledge of energy homeostasis and obesity physiology. We contributed to a study (3) looking at the effects of diet macronutrient content on energy expenditure, with the conclusion that macronutrient differences have a small effect. Finally we have summarized the current status of using melanocortin agonists clinically for obesity associated with proopiomelanocortin and discussed the implications for more common types of obesity (4).